Project Summary This Phase I SBIR proposal targets the development of recombinant human MG53 (rhMG53), a novel tissue repair protein, as a topical therapeutic candidate to facilitate healing of chronic wounds. Wound care represents a challenging problem to the public health, as no effective treatments for chronic non-healing wounds are available. MG53 is an essential component of the cell membrane repair machinery that protects against tissue injuries. Research and development efforts at TRIM-edicine, a university spin-off biotechnology company, have established that rhMG53 protein has great potential in facilitation of wound healing and reduction of scar formation targeting multiple cellular processes. The chemistry, manufacture and control (CMC) process for scale-up production of rhMG53 has been developed. Preliminary toxicological studies in rodent and dog models support the safety for rhMG53 in topical and intravenous applications. There is extensive evidence to support the efficacy for rhMG53 in treatment of cutaneous wounds in rodent and rabbit models. Based on these studies, TRIM-edicine initiated a pre-IND meeting with the FDA and obtained guidance from the Agency for developing rhMG53 as a topical agent to facilitate healing of chronic wounds. The goal of this SBIR project is to conduct the required pre-clinical studies testing the safety and efficacy of rhMG53 as a topical therapy, toward evaluating this agent in human subjects with wound healing problems. Studies proposed in this application will involve joint development efforts between TRIM-edicine and Wound Care Center at The Ohio State University. Specifically, we propose to produce sufficient rhMG53 proteins to support the IND-enabling topical formulation for rhMG53 with adequate shelf-life and activity (Aim 1), and then test the lead prototype formulation in a porcine model of chronic ischemic wounds to evaluate the safety and efficacy of rhMG53 as a topical therapy (Aim 2). Fulfillment of these studies is pivotal for our future development effort with testing rhMG53 in human clinical trials to facilitate healing of chronic wounds.